Our research is designed to determine whether target cells for the gonadotropin hormones exist in human/murine melanoma and ovarian cancer and, as such, whether the growth and differentiation of these neoplasms are modulated or dependent on these trophic hormones. Findings from this laboratory indicate that: (1)\various types of ovarian tumors of epithelial (n=35) and germ cell (n=3) origin do not display 125I-follicle stimulating hormone (FSH) or chorionic gonadotropin (CG) binding which is representative of a receptor interaction; (2)\in contrast, tumors of sex cord stromal origin may contain FSH binding sites reminiscent of gonadotropin receptors; and (3)\murinemelanoma contains binding sites for preparations of 125I-luteinizing hormone (LH) which are qualitatively distinct from LH-CG receptors found in gonadal tissues. The next year's aims are: (1)\to investigate further the presence of gonadotropin-sensitive adenylate cyclase in human ovarian cancers and melanoma and to correlate activity with the presence of specific binding sites for the gonadotropins; (2)\to assess the level of gonadotropins in human ovarian cancers and melanomas as a marker of ectopic hormone production and resultant occupancy of available gonadotropin receptors; and (3)\to continue characterization of LH binding sites in melanoma which are qualitatively distinct from those in normal gonadal tissue. Available gonadotropin receptors will be characterized from the specific binding of 125I-hLH, -hCG, and -hFSH to particulate preparations of tumor samples. Adenylate cyclase activity will be assessed from the conversion of [32P]-ATP to [32P]-cyclic AMP by tumor homogenates. Gonadotropin content in saline-\and acid-extracts of tumor samples will be assessed by radioimmunoassay and antibody-protein A precipitation. These studies will provide new information on the hormonal factors regulating and hormone synthesis by ovarian cancer and melanoma. As such, progress in this research may offer novel methods of therapy for these tumors which are related to the control of gonadotropin secretion and action. (C)